Compositions and methods for inhibition of hao1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression

A double stranded RNAi agent that inhibits expression of HAO1 in a cell, or a salt thereof,

• wherein said double stranded RNAi agent, or a salt thereof, comprises a sense strand and an antisense strand forming a double stranded region,
• wherein said sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequences of from any one of the nucleotide sequences of SEQ ID NO:1 SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:6 and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequences of SEQ ID NO:3 SEQ ID NO:4, SEQ ID NO:7, or SEQ ID NO:8,
• wherein all of the nucleotides of said sense strand comprise a modification selected from the group consisting of a 2′-O-methyl modification and a 2′-fluoro modification,
• wherein said sense strand comprises two phosphorothioate internucleotide linkages at the 5′-terminus,
• wherein all of the nucleotides of said antisense strand comprise a modification selected from the group consisting of a 2′-O-methyl modification and a 2′-fluoro modification,
• wherein said antisense strand comprises two phosphorothioate internucleotide linkages at the 5′-terminus and two phosphorothioate internucleotide linkages at the 3′-terminus, and
• wherein said sense strand is conjugated to one or more GalNAc derivatives attached through a branched bivalent or trivalent linker at the 3′-terminus.